Harris 2009.

Methods	Randomised controlled trial, parallel group
Participants	Total number of participants: 25 Baseline characteristics: Therapeutic cooling Age: mean (SD) 38.1 (± 15.0) years Gender M/F: 11/1 GCS on admission: mean (SD) 3.9 (± 1.7) Type of injury (closed/open): blunt 10; penetrating 2 No cooling Age: mean (SD) 33.2 (± 20.0) Gender M/F: 11/2 GCS on admission: mean (SD) 4.3 (± 2.1) Type of injury (closed/open): blunt 12; penetrating 1 Inclusion criteria: severe traumatic brain injury, GCS score ≤ 8, ≥ 18 years of age, required an ICP monitor and Foley catheter as part of routine treatment, able to receive the Discrete Cerebral Hypothermia cooling cap within 48 hours of hospital admission, participant’s family member or guardian spoke English to ensure proper informed consent Exclusion criteria: patient’s family member or guardian was unwilling or unable to sign an informed consent, physical placement of the cooling cap impeded routine treatment, patient’s core body temperature was ≤ 36°C at the time of initial assessment, treatment could not be initiated within 48 hours of admission Country: USA Setting: Level 1 trauma centre, hospital
Interventions	Therapeutic cooling Number of participants: 12 Method of cooling: Discrete Cerebral Hypothermia System (“the cooling cap”) Target temperature: target intracranial temperature 33 °C, target systemic temperature maintained above 36 °C using heating blankets Time of cooling: mean time in emergency department prior to study enrolment 4.6 (± 4.5) hours. (Note: exclusion criteria suggests could be up to 48 hours after admission) Duration of cooling: 24 hours Rewarming details: 0.5 °C every 3 hours for 24 hours (study hours 25 to 48). Cooling cap was removed after 48 hours. Site of measurement: intracranial and bladder temperatures No cooling Number of participants: 13 Method of temperature management: heating blankets Target temperature: 36°C Time of cooling: mean time in emergency department prior to study enrolment 7.2 (± 3.7) hours
Outcomes	Outcomes measured in study: temperature gradient, mortality (up to day 28), GOS (up to day 28), Functional Independence Measure, complications (respiratory failure, shock, septicaemia, decubitus ulcer, cardiac arrest)
Notes	Funding/declarations of interest: "no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper" Study dates: July 2006 to August 2007 Note: unfavourable outcome was reported as median maximum change in GOS during 28 study period. "No statistically significant intergroup difference in GOS‐determined morbidity"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomisation was determined by the Department of Biostatistics using computer‐generated random numbers" Participants stratified by GCS scores after randomisation
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias): mortality	Low risk	Lack of blinding unlikely to influence performance for this outcome
Blinding of participants and personnel (performance bias): GOS	Unclear risk	Unclear if lack of blinding would influence performance for this outcome
Blinding of outcome assessment (detection bias): mortality; pneumonia	Low risk	No details; lack of outcome assessor blinding is unlikely to influence outcome data
Blinding of outcome assessment (detection bias): GOS	Unclear risk	No details
Incomplete outcome data (attrition bias) All outcomes	High risk	Complete outcome data not available for 4 participants, and study has small sample size. Explanations given and patients still included in intention‐to‐treat analysis. Control group has a 23% loss
Selective reporting (reporting bias)	Unclear risk	Clinical trials registration or pre‐published protocol not reported. Insufficient information to make judgement
Other bias	Unclear risk	Baseline characteristics comparable. But statistically significant differences in time to study enrolment between two groups